phenotypic screening

Historically, drug discovery was based on screening compounds that led to desirable changes in the phenotype of a cell, tissue or organism. As our knowledge of the genes and pathways involved in diseases increased in the second half of the 20th century, the phenotypic approach to screening gradually fell out of favour.

The return to phenotypic screening has been pronounced since it was noted that 37% of the first-in-class drugs approved by the FDA between 1999 and 2008 were discovered as a result of phenotypic screening, compared to only 23% via target-based.

High-content phenotypic assays represent more physiologically-relevant screening models, albeit with a compromise on throughputs. Implementation challenges mean this approach has not been readily adopted within primary screening, where target-based screens predominate but don’t offer the same degree of biologically-relevant data.

In order to maximise the benefits of phenotypic screening and minimise your chances of missing a blockbuster hit, you need to screen your full compound library rather than using library subsets selected by biased target-based data.

However, to run full library phenotypic screens is challenging as it requires:

very rapid throughputs

miniaturisation to minimise cell and reagent costs

immediate hit identification

a manageable approach to data

The problem is that companies perceive they have to compromise between the convenience of target-based HTS and the relevance of phenotypic screening.

acumen® Cellista is the go-to system for practical, full library phenotypic screening with throughputs of over 2 million data points a week. It can scan and simultaneously analyse a whole well 1536-well microplate in only 5 minutes, offering robust high content data for immediate hit identification